Normal human chromosomes are being sorted for subsequent analysis of genetic variations. Genetic variations are being detected by quantitative analysis of end-labeled genomic fragments. The purpose of this work is to evaluate specific human populations for altered germinal mutation rates. To this end, the Michigan group has developed two-dimensional electrophoresis of DNA fragments obtained from restriction-enzyme-digested genomic DNA. This procedure permits the analysis, on a single preparation of about 2000 DNA fragments varying in size from 1.0 to 5.0 kb in the first dimension and 0.3 to 2.0 kb in the second dimension. With single chromosome types we have demonstrated that we can increase the resolution even further. This technology should be highly efficient in monitoring for mutations resulting in loss/gain/rearrangement events in DNA fragments distributed throughout the genome (Genomics 38, 124 (1996)).